Synthesis
The general procedure for the synthesis of 2-((tert-butoxycarbonyl)amino)-4-methoxy-4-oxobutanoic acid from 4-methyl DL-aspartic acid hydrogen ester is as follows:
Example 8 Synthesis of DL-2-tert-butoxycarbonylamino-succinic acid 4-methyl ester
To stirring DL-2-amino-succinic acid 4-methyl ester (dissolved in a solution of dioxane/H2O (2:1, 110 mL)) was added Na2CO3 (3.92 g, 0.037 mol). After CO2 release ceased, Na2CO3 (3.92 g, 0.037 mol) was added again, followed by Boc2O (8.87 g, 0.04 mol). The reaction mixture was stirred at 0 °C for 1 h (a white precipitate was formed within 30 min) and then continued to stir overnight at room temperature. After completion of the reaction, the solvent was removed under reduced pressure and the residue was washed with Et2O. The aqueous phase was acidified with saturated aqueous NaHCO3, then the pH was adjusted with NaHSO4 and extracted with Et2O. The organic phases were combined, dried with Na2SO4 and concentrated under reduced pressure to give 2-((tert-butoxycarbonyl)amino)-4-methoxy-4-oxobutanoic acid as a white solid (6.7 g, 74% yield).
